title: The effect of N-methyl-D-aspartate receptor antagonists on D,L-homocysteine thiolactone induced seizures in adult rats.
abstract: The aim of our study was to investigate the effects of ifenprodil and MK-801 on D,L-homocysteine thiolactone induced seizures in adult rats.Male Wistar rats were divided into following groups: 1. Saline-treated (C, n=10); 2. D,L-homocysteine thiolactone 8 mmol/kg, i.p. (H, n=7); 3. Ifenprodil 20 mg/kg i.p. (IF, n=8); 4. MK-801 0.5 mg/kg, i.p. (MK, n=8) and 5. Groups that received IF or MK 30 minutes prior to H (IFH, n=8 and MKH, n=8). Seizure behavior was assessed by incidence, latency, number and intensity of seizure episodes. Seizure severity was described by a descriptive scale with grades 0-4. Lethality in experimental group was recorded 90 min and 24 h upon D,L-homocysteine thiolactone administration.There were no behavioral signs of seizure activity in groups C, IF and MK.Pre-treatment with MK-801 (MKH) showed tendency to reduced incidence of convulsions, latency to the first seizure onset and the severity of seizure episodes, but statistical significance was not attained comparing to the H group. However, median number of seizure episodes was significantly decreased in MKH (p<0.05), comparing to the H group. On the other hand, ifenprodil (IFH) decreased the latency to the first seizure onset and increased the median number of seizure episodes (p<0.05). The majority of seizure episodes in IFH (72.1%, p<0.05) and MKH (73.1%, p<0.05) groups was grade 2 and significantly different comparing to the H (36.0%). Our findings suggest that MK-801 has a mild anticonvulsive effect on D,L-homocysteine thiolactone induced seizures in adult rats.
authors.affiliation: University of Belgrade, Laboratory for Neurophysiology, Institute of Physiology, School of Medicine 11 000 Belgrade, Serbia.
authors.forename: A
authors.initials: A
authors.lastname: Rašić-Marković
authors.forename: D
authors.initials: D
authors.lastname: Hrnčić
authors.forename: D
authors.initials: D
authors.lastname: Djurić
authors.forename: D
authors.initials: D
authors.lastname: Macut
authors.forename: H
authors.initials: H
authors.lastname: Lončar-Stevanović
authors.forename: Olivera
authors.initials: O
authors.lastname: Stanojlović
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy*
chemical_list: D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D006710:Homocysteine; D016291:Dizocilpine Maleate; C007957:homocysteine thiolactone; C010739:ifenprodil